latest trend of pharmaceutical and medical device …pharmaceuticals and medical devices agency 5...

Pharmaceuticals and Medical Devices Agency

Latest Trend of Pharmaceutical and Medical Device Regulation

in Japan

UZU ShinobuSenior Executive Director, PMDA

8th Joint Conference of Taiwan and Japan on Medical Products Regulation15th October 2020


Background andMain Theme of Revision of PMD Act

Pharmaceuticals and Medical Devices Act (PMD Act)*: the regulation of medical products in Japan‐ Mandatory review of the Act after the 5‐years implementation (PMD Act was implemented in 2013)‐ The review examines the results of the previous revision, trend of demography, innovation and future vision.‐ Expert Committee in the Health Sciences Council started review discussion from April, 2018.‐ The committee formulated the review report in December, 2018.

* The Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical devices

Background

Three themes were discussed:1.Ensuring early access to innovative pharmaceuticals & medical devices, and enhancing the safety measures

2.The role of community pharmacies and pharmacists, and the secure access to medicines3.Enhancing the systems to ensure legitimate manufacturing, distribution and sales of pharmaceuticals & medical devices (Qualification and dismissal of officers, levy surcharge for company)

Main Theme


Review of PMD Act

Possible provisions after amendment

(1) Streamline of Approval Process for early patient access① “Conditional Early Approval System” and “SAKIGAKE Review Designation” should

be legislated to clarify process and raise transparency.② New Approval system for Medical Devices to reflect the characteristics of medical

devices (considering innovative technologies; Big Data, AI etc.,)③ Clarification of clinical trials process and ensuring safety of subjects

(2) Introduction of new Quality Management System① Introduction of GMP and GCTP inspection per manufactory② Revision of current QMS inspection③ Introduction of Change Management Method for approved products concerning

Quality using PACMP

(3) Strengthen Safety Measures ① Provide electronic information of Package Inserts ② Increase traceability of pharmaceuticals and medical devices③ Utilize Patient Registry Data For safety measure

Main Points of Revised PMD Act


Type Designation criteriaPriority review 1. For severe diseases & orphan disease

2. Apparent improvement of medical careReview time is shortened 9 months from 12 months.

SAKIGAKE(Forerunner designation)

1. Innovative medical products2. For serious diseases3. Development & NDA in Japan: being world’s first or simultaneous with other countries4. Prominent effectiveness expected on non‐clinical and early phase clinical studies

Conditional Early Approval

* In addition to priority review1. Confirmatory clinical trials are not feasibility.2. Additional PV and Risk minimization are required as approval conditions.

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The Expected Pathways newly incorporated into the Revised PMD Act‐ Make more opportunities that Japan will be the first country to get approval‐


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Phase I/II

2 months 12 months

Strengthening post‐marketing safety measures

【Ordinary Review】

【Sakigake Scheme】

Consultation Phase Ⅲ Review

consultation

Non‐clinical/clinical

researchPhase I/II Consul

tation Phase Ⅲ

DesignationDesignation Prior Review Review

※Accept Phase III data after the application, if necessary.

consultation

Non‐clinical/clinical

research

1 month

6 months

②Prior Review

①Priority Consultation

③Priority Review

Approval

Approval

Accelerate Innovative drug access

Consideration of premium pricing under health insurance

Review reports will be translated into English preferentially.

SAKIGAKE shortens review time to 6 months without omitting data


Exploratory clinical trials*1 Approval

○To accelerate patient access to drugs with particularly high medical needs that treat serious diseases with limited treatment options, and difficult to conduct confirmatory clinical trials due to the small number of patients or long trial period, conditions such as post‐marketing surveillance to reconfirm the efficacy/safety shall be set at the time of approval in addition to a certain level of efficacy/safety verified in nonconfirmatory clinical studies.

○ At the same time, a scheme where re‐evaluation is promptly made based on the reconfirmation survey results to reflect on the safety measures shall be introduced.

Exploratory clinical trials*1

Adverse Drug Reaction ReportingPost-marketing surveillance

Application/Review

・Early application enabled by ensuring a certain level of efficacy and safety in nonconfirmatory clinical studies

・ Shorter review time through designation as priority review

■ Setting conditions by item based on data obtained at the time of approval.

・Data collection to reconfirm post‐marketing efficacy & safety(including real‐world data)・Setting requirements for facilities/physicians, etc.

Post-marketing surveillance Assess

-ment ADR reporting

* Real World Data: Various data collected in the actual clinical settings, different from clinical studies.

■Assessing quality/efficacy/safety of the drug based on the surveillance results during the re-examination period.

■Based on the assessment results, giving instructions to change the conditions or take additional safety measures.

Conditions for approval

Standard Review

Confirmatory clinical trials*2

*1. Small-scale, dose-finding clinical studies investigating drug efficacy and safety*2. Large-scale clinical studies investigating the efficacy and safety of an established dosing regimen

Conditional Early Approval System

ApprovalRe‐evaluation

Re‐evaluation

Application/Review

From 1 Sep. 2020

Legislation of “Conditional early approval system”(Drugs)


○When drugs are significantly insufficient for medical needs, including drugs whose dosage and administration have not been established for pediatric use, a system should be legislated for identifying them as “drugs for specific use”. . If they are identified, it should be legally clarified that they would be subject to priority reviews.

○The law provides for securing necessary funds and taking tax measures for drugs for specific use as well as current orphan drugsassurance of necessary funds to promote study and research (this condition is limited to cases where the number of patients related to the specific use is small).（※）with regard to tax incentives, it has been already positioned in the outline of the tax system revision in 2019.

Drugs for specific use

①Drugs are used for treatment of diseases belonging to the specific classification(※).※・Drugs are used for pediatric diseases and the

dosage and administration for pediatrics has not been included.

・Drug-resistant bacterial infection②The need is significantly insufficient for drugs related to the use.

③With regard to the use, they have particularly excellent value for use.

Specified requirements

Drugs having particularly high medical necessity Orphan drugs※

others

After revision

SAKIGAKE drugs

Drugs for specific use

PMD Act

Legally clarify that it will be subject to priority reviews

（※）The number of patients who may use the drug should be less than 50,000 in Japan, or the drugs should be indicated for difficult‐to‐treat diseases.

Legislation of “Drugs for Specific Use”from 1 Sep. 2020


(Reference) Approval system for drugs/medial devices

Cross-Check

Review

PACMP submission Check

Change application

Ordinary change procedure

Change procedure with PACMP

Make a partial change application with all the required data

PACMP preparation

○ A system to change approved items related to drug quality including manufacturing methods based on Post‐Approval Change Management Protocol (PACMP) shall be added.

○ Specific protocols are as follows:

• A Marketing Authorization Holder submits a post‐approval change plan, and PMDA reviews the plan and the MAH collects the actual data related to the change based on the plan.

• When the MAH actually changes the manufacturing method, it submits a notification of the change to PMDA. PMDA cross‐checks the notification with the plan.

Changes in the manufacturing method, evaluation method and acceptance criteria for the change are included in the plan. The authorities check the plan in advance.

⁎Companies need to collect sufficient information on a new manufacturing method when they prepare the PACMP. Thus MAHs’ ability to use innovative production techniques and to control the product quality can be improved. ⁎For applications requiring a long time to review, the cross‐check period after the change notification can be shortened. ⁎As the protocol is changed from application to notification, companies can flexibly set the time to change the production procedure and switch the products, ensuring effective supply chain management.

Shorter period for

the change

The authorities cross-check the implementation of the plan.

Change in the approved

items

Benefits of the system

Quality data collection/verification based on the PACMP

Change notification

Change in the approved

items

Quality data collection/verification based on the PACMP

Review of Change Procedure for Approved Items by Post‐Approval Change Management Protocol (PACMP) From 1 Aug., 2021


Clinical data collection Review

Approval

Expansion of indicationsReview

Current flow for expansion of indications

Changes in the approved items

Applic‐ation

Application for changes

Review

Earlier improvement

Data collection

Revised flow for expansion of indications

Data collection according to the plan

Notification of the plan

○ For medical devices planned to be modified*, a review system which enables continuous improvement shall be introduced by validating a change plan during the review process and quickly approving partial changes made within the planned scope.

* Including medical devices with AI which are expected to constantly evolve after the launch, improvements based on the real world data (RWD: data from actual clinical use) to be collected after the marketing, and additions of optional parts to increase the usability, etc.

Application for partial changes in the approved items after collecting all the necessary data

Whether the planned results are obtained or not is checked

Check

Building of a change plan for expansion of indications

Application or notification of

changes

Notification:•Changes in sizes, components, performance•Increased diagnostic performance based on the post‐marketing RWD

Valida‐tion

Clinical data collection

Building of a change plan for expansion of

indications

Changes in the approved

items

Expansion of indications

Approval

Applic‐ation

New Approval System Based on the Type of Medical DeviceNew Approval System Based on the Type of Medical DeviceNew Approval System Based on the Type of Medical Device

MAH・Wholesaler︓Provide hardcopy of labeling, if necessary 1) at initial delivery2) at the time of labeling revision

○○○○錠10mg

（株）××

処方箋医薬品

MAH Medical Institution ○○○○錠10mg使用上の注意改訂

のお知らせ

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Medical Institution:Get the latest labeling via e-labeling access code /website

MR・Wholesaler

MAH︓Prepare a website to provide the latest labeling

○○○○錠10mg

~~~~~~~

【警告】

【効能・効果】

~~~~~~~~~

~

【使用上の注意】

~~~~~

【用法・用量】

~~~~~

~~~~~~~~~~~~~~~~~~~~

~~~~~

~~~~~

Electronic information

hardcopy of labeling

MAH︓Print e-labeling access code such as QR code which can be accessed to labeling on packages

Introduction of E‐labeling


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Approved Drug for COVID-19 Approved IVDs for COVID-19 Allowed to start clinical trials without waiting period of 30

days after notification

３）For non-COVID-19 Products

２）For COVID-19 Products

https://www.pmda.go.jp/english/about-pmda/0002.html

１）PMDA statements (six statements as of July 15th, 2020)

Actions for COVID‐19

Provided information on how to manage clinical trials


PMDA statements on COVID-19

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PMDA pledge to tackle COVID-19 PandemicPMDA Takes Further Steps to Speed up Clinical Development of COVID-19 ProductsFour IVDs Approvals for COVID-19 and Response to the Increased Ventilator DemandSpecial Approval for Emergency on Remdesivir for COVID-19First Approval of Antigen Test for COVID-19For Your Access to Japanese Clinical Trial/Clinical Research Information

6 statements issued:

As of July 15th, 2020

PMDA statements on COVID‐19


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Provided information to sponsors and clinical trial site for non-COVID-19 products on alternative measures that can be taken when the process predetermined in the study protocol is not deemed feasible due to COVID-19

https://www.pmda.go.jp/english/int-activities/0002.pdf

Q&As on how to manage clinical trials for non COVID‐19 products


Cooperation with TFDA

The 7th Joint Conference of

Taiwan and Japan on Medical Products

Regulation in Tokyo (1 Oct. ‐2

Oct. 2019）

ATC SeminarsGRM

In Taipei(Sep 26‐28,2018,

17‐19, Sep, 2019)

2018 Joint New Drug‐GBO WG Meeting of Taiwan and Japan in

Taipei

(8th May, 2018)2018 Multi Regional Clinical Trial (MRCT)

Workshop in Taipei (9th‐10th May 2018)

Cooperation with TFDA

多謝Thank you!

Let’s work together for patients in Taiwan/Japan

and also in the world !

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